ArticleOncogene2021
Prostate cancer castrate resistant progression usage of non-canonical androgen receptor signaling and ketone body fuel.
Article in Oncogene, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 2 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 2 syntheses or guidelines pooled it, 28 citations in OpenAlex.
- Urinary and cellular volatile organic compounds as biomarkers for urological cancers: a systematic review of GC-MS-based volatolomics.Metabolomics : Official journal of the Metabolomic Society · 2026Pooled it
- Pre-diagnostic circulating untargeted metabolomics and risk of overall and clinically significant prostate cancer: a systematic review and meta-analysis.British journal of cancer · 2026Pooled it
- Metformin for patients with metastatic prostate cancer starting androgen deprivation therapy: a randomised phase 3 trial of the STAMPEDE platform protocol.The Lancet. Oncology · 2025Trial
- Ketogenic Diet as an Adjuvant in Epithelial Cancers: Mechanisms, Model Systems, and Translational Opportunities.Cancers · 2026Review
- Isoleucine and valine promote prostate cancer progression via propionyl-CoA-mediated cholesterol metabolism.Nature metabolism · 2026Article
- Histone methyltransferase KMT2D promotes castration-resistant prostate cancer progression by reactivating AR through FOXA1.Oncogene · 2026Article
- The significance of the ketolytic gene OXCT1 in metabolism, intracellular signaling and disease development.Cellular and molecular life sciences : CMLS · 2026Review
- Cross-population metabolome-wide Mendelian randomization study of prostate cancer risk.Research square · 2026Article
- Role of the cross-regulation between Wnt pathway activation and androgen receptor signaling in prostate cancer treatment resistance.Cell death and differentiation · 2026Article
- Identification of biomarkers for non-invasive diagnosis and risk stratification in prostate cancer using NMR-based metabolomics and machine learning.NPJ precision oncology · 2026Article
- Emerging insights into the role of BDH1 in the pathogenesis of human cancer.Frontiers in oncology · 2026Review
- Mitochondrial convergence of ferroptosis and cuproptosis in castration-resistant prostate cancer: From metabolic vulnerabilities to therapeutic targeting.BBA advances · 2026Review
- The Function and Mechanism of OXCT1 in Tumor Progression as a Critical Ketone Body Metabolic Enzyme.Biomolecules · 2025Review
- PKA-driven SPP1 activation as a novel mechanism connecting the bone microenvironment to prostate cancer progression.Oncogene · 2025Article
- An NMR-Based Metabolic Signature to Identify Clinically Significant Prostate Cancer in Patients Undergoing Biopsy.The Journal of clinical endocrinology and metabolism · 2025Article
- Anti-cancer role of curcumin in prostate cancer cells via regulation of m6A-modified circ0030568-FMR1 signaling pathway.Translational andrology and urology · 2024Article
- miR-1202 regulates BPH-1 cell proliferation, apoptosis, and epithelial-to-mesenchymal transition through targeting HMGCL.Acta biochimica et biophysica Sinica · 2024Article
- Integrative Molecular Analyses of the MD Anderson Prostate Cancer Patient-derived Xenograft (MDA PCa PDX) Series.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Integrative Metabolomic Analysis of Serum and Selected Serum Exosomal microRNA in Metastatic Castration-Resistant Prostate Cancer.International journal of molecular sciences · 2024Article
- BDH1-mediated LRRC31 regulation dependent on histone lysine β-hydroxybutyrylation to promote lung adenocarcinoma progression.MedComm · 2023Article
Corrections and comments
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Authors and funding
20 authors at 2 institutions in 2 countries.
Funding
Abstract
Prostate cancer (PCa) that progresses after androgen deprivation therapy (ADT) remains incurable. The underlying mechanisms that account for the ultimate emergence of resistance to ADT, progressing to castrate-resistant prostate cancer (CRPC), include those that reactivate androgen receptor (AR), or those that are entirely independent or cooperate with androgen signaling to underlie PCa progression. The intricacy of metabolic pathways associated with PCa progression spurred us to develop a metabolism-centric analysis to assess the metabolic shift occurring in PCa that progresses with low AR expression. We used PCa patient-derived xenografts (PDXs) to assess the metabolic changes after castration of tumor-bearing mice and subsequently confirmed main findings in human donor tumor that progressed after ADT. We found that relapsed tumors had a significant increase in fatty acids and ketone body (KB) content compared with baseline. We confirmed that critical ketolytic enzymes (ACAT1, OXCT1, BDH1) were dysregulated after castrate-resistant progression. Further, these enzymes are increased in the human donor tissue after progressing to ADT. In an in silico approach, increased ACAT1, OXCT1, BDH1 expression was also observed for a subset of PCa patients that relapsed with low AR and ERG (ETS-related gene) expression. Further, expression of these factors was also associated with decreased time to biochemical relapse and decreased progression-free survival. Our studies reveal the key metabolites fueling castration resistant progression in the context of a partial or complete loss of AR dependence.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.